Shiro Koizuka

The monoamine-mediated antiallodynic effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a rat model of neuropathic pain.

Antidepressants are often used to treat neuropathic pain. In the present study, we determined the antiallodynic effects of selective monoamine reuptake inhibitors in the spinal cord in a rat model of neuropathic pain. Mechanical allodynia was produced by tight ligation of the left L5 and L6 spinal nerves and determined by applying von Frey filaments to the left hindpaw. A serotonin noradrenaline reuptake inhibitor, milnacipran, a selective serotonin reuptake inhibitor, paroxetine, or a selective noradrenaline reuptake inhibitor, maprotiline, was administered intrathecally via a chronically implanted catheter. Milnacipran produced dose-dependent antiallodynic effects at doses between 3 &mgr;g and 100 &mgr;g. The effect lasted for 7 h after injection of 100 &mgr;g (P < 0.05). The antiallodynic effect of 30 &mgr;g of milnacipran was attenuated by intrathecal coadministration of 30 &mgr;g of yohimbine, an α2-adrenoceptor antagonist, 30 &mgr;g of methysergide, a serotonin receptor antagonist, or 30 &mgr;g of atropine, a muscarinic receptor antagonist (P < 0.01, respectively). Intraperitoneal administration of milnacipran had no antiallodynic effects at doses of 3 to 30 mg/kg. Antiallodynic effects were not produced by intrathecal administration of paroxetine (10 to 100 &mgr;g) or maprotiline (10 to 100 &mgr;g). These findings suggest that simultaneous inhibition of serotonin and noradrenaline reuptake in the spinal cord is essential to mediate antiallodynic effects. Milnacipran might be effective for suppression of neuropathic pain.

Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats.

PurposeSystemic ketamine suppresses several types of chronic pain. Although ketamine is used as a general anesthetic agent, the analgesic effect of systemic ketamine for early-stage postoperative pain is not clear. We investigated the efficacy and mechanism of systemic ketamine in a rat model of postoperative pain.MethodsAn incision was made in the plantar aspect of the left hind paw in male Wistar rats. Mechanical hypersensitivity was measured using calibrated von Frey filaments. The anti-hypersensitivity effect of systemic or intrathecal administration of ketamine was determined every hour after making the incision. We examined the effects of intrathecal pretreatment with yohimbine, an ?2-adrenoceptor antagonist, and methysergide, a serotonergic receptor antagonist, on the anti-hypersensitivity effect of ketamine. We also examined the effect of systemic ketamine on the c-fos immunoreactivity in the spinal cord.ResultsSystemic administration of ketamine at doses from 3 to 30 mg·kg-1 produced anti-hypersensitivity effects in a dose-dependent manner. Intrathecal administration of ketamine had no effect. There was no significant difference between effects of pre- and post-incisional administration. Intrathecal pretreatment with yohimbine (10 μg) or methysergide (15 μg) completely reversed the anti-hypersensitivity effects of systemic ketamine. Systemic ketamine reduced fos expression in laminae I-II in the dorsal horn of the lumbar spinal cord ipsilateral to the paw incision.ConclusionsThe results suggest that systemic administration of ketamine perioperatively suppresses early-stage postoperative pain via monoaminergic descending inhibitory pathways.RésuméObjectifLa kétamine intravasculaire supprime certaines douleurs chroniques. Utilisée comme anesthésique général, son effet analgésique pour la douleur postopératoire de stade précoce n’est toutefois pas clair. Nous avons vérifié l’efficacité et le mécanisme de la kétamine intravasculaire chez un modèle rat de douleur postopératoire.MéthodeUne incision a été faite dans la partie plantaire de la patte arrière gauche de rats mâles Wistar. L’hypersensibilité mécanique a été mesurée à l’aide de filaments von Frey calibrés. L’effet d’antihypersensibilité de la kétamine vasculaire ou intrathécale a été déterminé toutes les heures après l’incision. Nous avons étudié les effets du prétraitement intrathécal avec yohimbine, un antagoniste des récepteurs ?2-adrénergiques, et méthysergide, un antagoniste des récepteurs sérotoninergiques, sur l’effet anti-hypersensibilité de la kétamine. Nous avons aussi vérifié l’effet de la kétamine intravasculaire sur l’immunoréactivité des c-fos dans la moelle épinière.MRésultatsL’administration intravasculaire de kétamine en doses de 3 à 30 mg·kg-1 a produit des effets d’anti-hypersensibilité reliés à la dose. La kétamine intrathécale n’a pas eu d’effet. Il n’y avait pas de différence significative entre les effets de l’administration pré-incisionnelle et post-incisionnelle. Le prétraitement intrathécal avec yohimbine (10 μg) ou méthysergide (15 μg) a complètement renversé les effets d’anti-hypersensibilité de la kétamine intravasculaire. La kétamine intravasculaire a réduit l’expression de fos dans la lame I-II de la corne supérieure de la moelle épinière lombaire homolatérale à l’incision de la patte.ConclusionLes résultats suggèrent que l’administration intravasculaire préopératoire de kétamine supprime la douleur postopératoire de stade précoce par des voies inhibitrices descendantes monoaminergiques.

Thermogangliolysis of the Gasserian ganglion under computed tomography fluoroscopy.

Gasserian ganglion block is an established treatment for trigeminal neuralgia. A landmark approach assisted by X-ray fluoroscopy is the most common method; however, visualization of the foramen ovale is difficult in some cases. Here we report two cases in which a novel technique using modern computed tomography (CT) fluoroscopy was employed. A 63-year-old woman suffering pain in the maxillary nerve area was treated by thermogangliolysis under CT fluoroscopy. The patient was positioned on a CT stage with the head in an overhanging position. The CT gantry was set at an oblique angle to obtain a coronal view of the foramen ovale. The safest and shortest route to the foramen was designed using the CT image and a 22-gauge insulated needle was advanced following the designed route under CT fluoroscopy. The effect of the nerve block was estimated by injection of a test dose of mepivacaine, after which the ganglion was thermally coagulated at 90°C. Satisfactory analgesia was obtained in this case without any complications. Another patient (65 years old) was also treated by the same technique, and satisfactory pain relief was obtained. In conclusion, CT fluoroscopy-guided Gasserian ganglion thermolysis is considered a safe, quick, and effective treatment for trigeminal neuralgia.

Percutaneous radio-frequency thermocoagulation of the Gasserian ganglion guided by high-speed real-time CT fluoroscopy

IntroductionAlthough Gasserian ganglion block is an established treatment for trigeminal neuralgia, the foramen ovale cannot always be clearly visualized by classical X-ray radiography. We present a new method for percutaneous radio-frequency thermocoagulation of the Gasserian ganglion, in which computed tomography (CT) fluoroscopy is used to guide needle placement.MethodsIn the present study, 15 patients with trigeminal neuralgia underwent percutaneous radio-frequency thermocoagulation of the Gasserian ganglion guided by high-speed real-time CT fluoroscopy.ResultsTrigeminal neuralgia was improved in all patients after treatment without any severe complications. Moderate dysesthesia occurred in only one case.ConclusionCT fluoroscopy-guided percutaneous radio-frequency thermocoagulation of the Gasserian ganglion was safe, quick, and effective for patients with intractable idiopathic trigeminal neuralgia.

Percutaneous radiofrequency lumbar facet rhizotomy guided by computed tomography fluoroscopy

X-ray fluoroscopy-guided percutaneous radiofrequency facet rhizotomy is used to treat chronic low back pain. The traditional fluoroscopic approach to the medial branch of the posterior rami, however, is associated with a small incidence of complications. We describe a new method for radiofrequency lumbar facet rhizotomy in which computed tomography (CT) fluoroscopy is used to guide needle placement. Three patients with chronic intractable low back pain underwent CT fluoroscopy-guided percutaneous facet rhizotomy. After the safest and shortest route to the target site was determined on the CT image, the needle was advanced along the predetermined route under real-time CT fluoroscopy. When the needle tip was located at the target site, electrical stimulation was applied to verify proper electrode placement. After confirming the clinical effect and lack of complications under test block with a local anesthetic, denervation was performed using radiofrequency current. Pain scores of all patients were reduced after the procedure without any complications such as paralysis or neuritic pain. None of the patients complained of severe discomfort during the procedure. CT fluoroscopy-guided percutaneous lumbar facet rhizotomy appears to be safe, fast, and effective for patients with lumbar facet pain.

Percutaneous Radiofrequency Mandibular Nerve Rhizotomy Guided by High-Speed Real-Time Computed Tomography Fluoroscopy

We present a new method of percutaneous radiofrequency mandibular nerve rhizotomy for pain relief in the mandibular region, in which needle placement is guided by high-speed real-time computed tomography (CT) fluoroscopy. Eleven patients (13 procedures) with idiopathic trigeminal neuralgia underwent the procedure. CT fluoroscopy simultaneously provided 3 slices (1-mm interval series, craniocaudally) in 1 fluoroscopic view, allowing for accurate needle placement. Trigeminal neuralgia improved in all patients without severe complications. The mean numerical rating scales of pain intensity (±SD) decreased from 6.5 (±1.8, pretreatment) to 1.8 (±1.7, 1 month after treatment) and to 0.9 (±1.0, 3 months after treatment). Our limited-case series suggests potential advantages for the new CT fluoroscopy guidance, but these findings await confirmation from randomized controlled trials and large-case series.

Anatomic analysis of computed tomography images obtained during fluoroscopic computed tomography-guided percutaneous lumbar sympathectomy

PurposeThe fluoroscopic computed tomography (CT)-guidance technique increases the accuracy and safety of needle placement for percutaneous lumbar sympathectomy. The aim of the present study was to provide anatomic data from CT images and to discuss the safest route for needle insertion.MethodsWe retrospectively analyzed CT images that were obtained from 25 patients (14 men, 11 women; 37—89 years of age [mean, 68.4 years]) during fluoroscopic CT-guided percutaneous lumbar sympathectomy. The anatomy around the inserted needle was measured and the correlations between patient characteristics and the procedure-related distances were assessed.ResultsThe distance from the midline (spinous process) to the entry point and the depth to the target site correlated with body size, especially height and weight. The maximal distance from midline to the insertion point in the range of safe needle insertion at L2 was less than 7.0 cm in approximately 20% of the patients.ConclusionThe present study was performed to determine the anatomic details required to guide safe percutaneous lumbar sympathectomy based on CT images. The use of CT guidance is recommended for lumbar sympathectomy, especially at the L2 spinal level.

CT-guided nerve block: a review of the features of CT fluoroscopic guidance for nerve blocks

Nerve blocks are an attractive interventional therapy in pain medicine. Several image guidance methods are available to secure the safety, accuracy, and selectivity of the nerve block. Computed tomography (CT) guidance provides a clear view of the vital viscera and vessels that should be avoided by the needle, and accurate placement of the needle tip before neuro-destructive procedures. A recent advance in CT technology is multi-slice CT fluoroscopy, which allows for rapid and easy correction of needle tip placement during insertion. To reduce the radiation dose for both patients and staff, the lowest radiation setting, intermittent quick-check fluoroscopy, and shortening of the planning scan should be used. Preliminary CT scanning with excellent spatial resolution may facilitate the application of CT fluoroscopic guidance to various types of nerve blocks. Here we review celiac plexus and splanchnic nerve blocks, trigeminal nerve block, neurolytic sympathectomy, and spinal intervention performed under CT guidance. Additional large-scale studies are needed to optimize the use of image guidance, especially CT fluoroscopy guidance, for nerve blocks.

A novel bFGF-GH injection therapy for two patients with severe ischemic limb pain

Severe ischemic pain is difficult to treat with a single therapy. Although modern angiogenic therapies have been used in patients with peripheral arterial occlusive diseases, a regimen combining novel angiogenic therapy and classic nerve blocks, including sympathectomy, has not been discussed to date. In this case report, we present two patients with peripheral arterial occlusive disease who were first treated with medication and lumbar sympathectomy, and then with a novel gelatin hydrogel drug-delivery system loaded with basic fibroblast growth factor. The gelatin hydrogel combined with recombinant basic fibroblast growth factor was injected intramuscularly into the ischemic limbs. In the first patient, with arteriosclerosis obliterans, a foot ulcer was healed, and the original score for resting pain (visual analogue scale, 5/10) was decreased to 0/10. In the second patient, with Buerger’s disease, a large toe ulcer was healed, and his resting pain (visual analogue scale, 8/10) was decreased to 1/10. Some other parameters, such as skin surface temperature, transcutaneous oxygen partial pressure, and pain-free walking distance, were also improved in both patients after the combined therapy. A multimodal approach is necessary to treat severe ischemic pain. Novel angiogenic therapy combined with nerve blocks seems to be a promising option in patients with severe pain.

Oral etodolac, a COX-2 inhibitor, reduces postoperative pain immediately after fast-track cardiac surgery

PurposeThe present study was designed to evaluate the efficacy of a cyclooxygenase (COX)-2 inhibitor, etodolac, on postoperative pain after fast-track cardiac surgery, and to examine the changes in plasma etodolac concentration after oral administration.MethodsThirty patients scheduled for elective coronary artery bypass grafting (CABG) surgery were randomly assigned preoperatively in a double-blind fashion to receive either vehicle (n = 15) or etodolac 400 mg (n = 15) via a gastric tube at the end of the surgery. Standardized fast-track cardiac anesthesia was used. In both groups, postoperative pain was treated with buprenorphine suppository. Visual analogue pain scores (VASs) were recorded immediately after extubation and at 24 h after surgery. Plasma etodolac concentration was measured at 1, 2, and 6 h after administration (n = 8).ResultsNo difference was detected in time to extubation between the etodolac group (209 ± 85 min, mean ± SD) and the vehicle group (207 ± 98 min). VASs were significantly lower in the etodolac (2.3 ± 2.1) vs the vehicle group (5.8 ± 2.0) immediately after extubation (P = 0.009), but no difference was detected in pain scores at 24 h after surgery, or in the amount of buprenorphine administered in the intensive care unit (ICU), or in the incidence of side effects. Plasma etodolac concentration was within the pharmaceutically recommended range at 1 h, 2 h, and 6 h after administration.ConclusionThe oral use of etodolac with rectal buprenorphine reduces pain scores immediately after cardiac surgery without an increase in side effects.